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Impaired Spike Timing Dependent Cortico-Cortical Plasticity in Alzheimer's Disease Patients
Francesco Di Lorenzo1, Viviana Ponzo1, Caterina Motta1
1Department of Behavioural and Clinical Neurology, Non-invasive Brain Stimulation Unit, Santa Lucia Foundation IRCCS, Rome, Italy.
Background:
Mechanisms of cortical plasticity have been recently investigated in Alzheimer's disease (AD) patients with transcranial magnetic stimulation protocols showing a clear impairment of long-term potentiation (LTP) cortical-like plasticity mechanisms.
Objective:
We aimed to investigate mechanisms of cortico-cortical spike-timing dependent plasticity (STDP) in AD patients investigating the connections between posterior parietal cortex (PPC) and primary motor cortex (M1).
Methods:
We used a cortico-cortical paired associative stimulation (cc-PAS) protocol to repeatedly activate the connection between PPC and M1 of the left-dominant hemisphere in a sample of fifteen AD patients and ten age-matched healthy subjects. PPC transcranial magnetic stimulation preceded (ccPAS +5) or followed M1 stimulation (ccPAS - 5) by 5 ms. Motor-evoked potentials (MEPs) were collected to assess the time course of the after effects of cc-PAS protocol measuring MEP amplitude as index of cortico-cortical associative plasticity.
Results:
In healthy subjects, ccPAS - 5 protocol induced the expected long-lasting increase of MEP amplitude compatible with LTP-like cortical plasticity while PAS +5 protocol induced the opposite effect. AD patients did not show any significant modification of the amplitude of MEP after both ccPAS protocols.
Conclusions:
Our study shows that in AD patients the time-locked activation of human cortico-cortical connections is not able to form STDP, reflecting an impairment of a multi-factor plasticity process.